Professional Documents
Culture Documents
Marianne Ong
Jie Han
Nikos Mattheos
Bjarni E. Pjetursson
Alex Yi-Min Tsai
Ignacio Sanz
May C.M. Wong
Niklaus P. Lang
on Behalf of the ITI
Antibiotic Study Group
Effect of systemic antibiotics on
clinical and patient-reported outcomes
of implant therapy a multicenter
randomized controlled clinical trial
Authors afliations:
Wah Ching Tan, Marianne Ong, National Dental
Centre Singapore, Singapore, Singapore
Jie Han, Peking University School of Stomatology,
Beijing, China
Nikos Mattheos, Grifth University, Gold Coast,
Queensland, Australia
Nikos Mattheos, May C.M. Wong, Niklaus P. Lang,
Faculty of Dentistry, The University of Hong Kong,
Hong Kong SAR, China
Bjarni E. Pjetursson, Faculty of Odontology,
University of Iceland, Reykjavik, Iceland
Alex Yi-Min Tsai, Department of Periodontology,
School of Dental Medicine, National Taiwan
University, Taipei, Taiwan
Ignacio Sanz, Universidad Complutense de Madrid,
Madrid, Spain
ETEP Research Group
Corresponding author:
Dr. Wah Ching Tan, BDS, MDS, Dr.med.dent.
Consultant, National Dental Centre Singapore
5 Second Hospital Avenue
Singapore 168938
Singapore
Tel.: +65 98553559
Fax: +65 64766071
e-mail: drwahching@yahoo.com.sg
Key words: complications, dental implants, failures, implant dentistry, patient-reported
outcomes, success, survival, systemic antibiotics
Abstract
Objectives: To determine the effect of various systemic antibiotic prophylaxis regimes on patient-
reported outcomes and postsurgical complications in patients undergoing conventional implant
installation.
Material and methods: Three hundred and twenty-nine healthy adults in need of conventional
implant installation were randomly assigned to one of four groups: (i) preoperatively 2 g of
amoxycillin 1 h before surgery (positive control, PC), (ii) postoperatively 2 g of amoxycillin
immediately following surgery (test 1, T1), (iii) preoperatively 2 g of amoxycillin 1 h before and
500 mg thrice daily on days 2 and 3 after surgery (test 2, T2), (iv) preoperatively 2 g of placebo 1 h
before surgery (negative control, NC). Subjects were examined clinically by blinded examiners over
8 weeks after implant installation. In addition, Visual Analogue Scales (VAS) for pain, swelling,
bruising and bleeding were obtained over 14 days. ANOVA was performed for the VAS. Chi-square
tests were applied for postsurgical complications.
Results: All VAS scores were low for all groups and decreased over time (P < 0.001). There were no
signicant differences for the VAS scores between the various groups at any time point (P > 0.05).
There was only a signicant difference in ap closure at week 4, where NC had 5% of the subjects
not achieving complete wound closure compared to 0% for the three other groups (P = 0.01), with
no other signicant differences for any postsurgical complications (P > 0.05).
Conclusion: For standard single implant placement, prophylactic systemic antibiotics either before
or after, or before and after the surgical procedure do not improve patient-reported outcomes or
prevalence of postsurgical complications.
The use of prophylactic antibiotics against
postsurgical infection has largely been advo-
cated. However, the effects of such measures
remain obscure, and controversial benecial
outcomes have been reported in randomized
controlled clinical trials so far for oral surgi-
cal procedures (Monaco et al. 2009; Siddiqi
et al. 2010; Pasupathy & Alexander 2011). In
the eld of oral implant dentistry, the use of
systemic antibiotics remains a controversial
issue, and various antibiotic regimes have
been propagated without providing scientic
evidence for them. Some authors (Laskin
et al. 2000) reported higher survival rates
with the application of preoperative antibiot-
ics, while others (Gynther et al. 1998) found
no difference in postoperative infection and
survival rates of implants with pre- and post-
treatment antibiotics when compared to a
control group without them. Moreover, no
additional benets were found with the use
of antibiotics when compared to controls in a
recent randomized controlled clinical trial
(Abu-Taa et al. 2008). No signicant advan-
Conicts of interest: The authors declare no conict of
interest.
Date:
Accepted 24 November 2012
To cite this article:
Tan WC, Ong M, Han J, Mattheos N, Pjetursson BE, Tsai
AY-M, Sanz I, Wong MCM, Lang NP. Effect of systemic
antibiotics on clinical and patient-reported outcomes of
implant therapy a multicenter randomized controlled
clinical trial.
Clin. Oral Impl. Res. 25, 2014, 185193
doi: 10.1111/clr.12098
2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd 185
tages pertaining to postsurgical infection
were found with the use of perioperative
antibiotics for implant surgeries, provided
proper asepsis was established. Furthermore,
a multicenter placebo-controlled randomized
clinical trial (RCT) (Anitua et al. 2009) on
antibiotic prophylaxis with placement of sin-
gle dental implants conrmed no statistically
signicant differences for postsurgical infec-
tion, adverse events, and implant failures
between the groups.
These two RCTs were analyzed together
with two further RCTs from Italy (Esposito
et al. 2008, 2010a) in a recent Cochrane sys-
tematic review (Esposito et al. 2010b) with a
follow-up of at least 3 months comparing var-
ious prophylactic antibiotic regimes against
administration of a placebo. A statistically
signicantly higher number of patients with
implant failures was reported in the placebo
group, with a risk ratio of 0.4. The authors
concluded that there is some evidence sug-
gesting that the use of preoperative antibiotics
may reduce implant failures. It has to be real-
ized, however, that the degree of oral cleanli-
ness prior to implant installation was not
well documented in these studies.
At present, there is still a lack of large-
scale multicenter studies to support or refute
the need of antibiotic prophylaxis with con-
ventional implant placement. Some authors
recommended antibiotic prophylaxis with the
procedure based on cohort studies and anec-
dotal experience (Dent et al. 1997). With the
increasing demand for oral implants world-
wide and the development of antibiotic resis-
tance due to indiscriminate usage, the use of
antibiotics with conventional implant ther-
apy should be reevaluated and proper guide-
lines for implant installation established.
The question of whether or not the potential
benet of antibiotic prophylaxis with conven-
tional implant therapy outweighs the risk of
developing antibiotic resistance remains to
be determined. Moreover, there are no data
on the effect of perioperative administration
of systemic antibiotics in implant surgery on
patient-reported outcomes.
As demonstrated in a retrospective cohort
study (Powell et al. 2005), the prevalence of
infection following periodontal surgery was
low (2.09%). It was concluded that, although
perioperative antibiotics were commonly
used when performing regenerative and
implant procedures, data from this and other
studies suggested that there may be no bene-
t in using antibiotics for the sole purpose of
preventing postsurgical infections. Likewise,
it may be assumed that the use of periopera-
tive antibiotics in implant installation may
be of questionable value owing to the low
prevalence of infection associated with
implant installation.
Based on the limitation of the present evi-
dence available due to the lack of RCTs with
a large subject pool, there is no clear evi-
dence to recommend or contraindicate the
use of antibiotics to prevent infections with
oral implant placement. Neither is there any
established protocol of pre-, peri-, or postop-
erative administration of antibiotics.
Hence, the aims of the present multicenter
RCT were to determine the effects of various
systemic antibiotic prophylaxis regimes on
patient-reported outcome measures (PROMs)
and prevalence of postsurgical complications
in patients undergoing conventional implant
installation.
Material and methods
Subject population
Three hundred and twenty-nine healthy
adults were consecutively admitted to seven
study centers (National Dental Centre Singa-
pore (NDC), Singapore; The University of
Hong Kong, Faculty of Dentistry, Hong Kong
SAR; Peking University School of Stomatolo-
gy, Beijing, PR China; Grifth University,
Gold Coast, Queensland, Australia; Universi-
dad Complutense de Madrid, Madrid, Spain;
National Taiwan University, Taipei, Taiwan
& University of Iceland, Reykjavik, Iceland)
worldwide for conventional oral implant
therapy. The subjects were recruited between
August 2009 and October 2011.
Ethical aspects
The study protocol was submitted to and
approved by the respective institutional
review boards of the seven institutions. The
subjects were all informed about the purpose
of the study and the risks and benets associ-
ated with it. Informed consent was obtained
for all patients.
The following admission criteria to the
study were observed:
Inclusion criteria
a Medically healthy adults (ASA classica-
tion III), aged 19 years
b Preferably nonsmokers or previous smokers
(quit 5 years), light smokers with <20
cigarettes/day
c No allergies to amoxycillin or penicillin
antibiotics
d Single tooth edentulous space in the max-
illa or mandible with adequate pristine
bone for a standard oral implant placement
without the need of simultaneous bone
augmentation (bucco-lingual dimension
7 mm, mesio-distal dimension 7 mm
and height 8 mm)
Exclusion criteria
Subjects with any of the following exclusion
criteria at baseline were excluded from the
study:
a Medically compromised subjects (ASA clas-
sication IIIV)
b Subjects requiring antibiotic prophylaxis
prior to dental treatment
c Subjects aged <19 years
d Heavy smokers or previous heavy smokers
(quit <5 years; 20 cigarettes/day)
e Allergic to amoxycillin or penicillin antibi-
otics
f Use of any form of antibiotics in the last
3 months
g Pregnant, intend to conceive or breast-feed-
ing woman
h Single tooth edentulous space in the max-
illa or mandible with inadequate pristine
bone volume for standard oral implant
placement, with a possible need for bone
augmentation (bucco-lingual dimension
<7 mm, mesio-distal dimension <7 mm,
and height <8 mm).
The interventions involved conventional
implant installation with or without antibi-
otic prophylaxis. The oral implants were
placed into pristine bone, without any simul-
taneous bone augmentation. Only one
implant system (Straumann
Institute, Basel,
Switzerland) was used to minimize confound-
ing factors that might affect the outcome. The
implants used had a moderately rough (SLA)
surface and were in the range of 812 mm in
length. The diameters of the implants were
3.3, 4.1 or 4.8 mm. The implants were either
Standard Plus
or Bone Level
implants. A
one-stage implant installation protocol was
employed with the placement of healing abut-
ments, without the need for a second-stage
procedure to expose the implant.
Investigator calibration
The study was a blinded randomized con-
trolled clinical trial (RCT) with four treat-
ment arms. Prior to commencement of the
study, a 2-day investigator and examiner
standardization and calibration meeting was
held at the National Dental Centre Singa-
pore, Singapore.
Clinical procedures
The subjects were randomly assigned to one
of four groups (2 test and 2 control groups):
186 | Clin. Oral Impl. Res. 25, 2014 / 185193 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
Tan et al Systemic antibiotics and implant dentistry
Group 1 (positive control, PC): 2 g of
amoxycillin preoperatively, 1 h prior to
conventional implant placement.
Group 2 (test 1, T1): 2 g of amoxycillin
immediately postoperatively.
Group 3 (test 2, T2): 2 g of amoxycillin
preoperatively, 1 h prior to implant place-
ment and 500 mg three times a day
(8 hourly) on days 2 and 3.
Group 4 (negative control, NC): 2 g of a pla-
cebo preoperatively, 1 h prior to implant
placement without any antibiotics.
The medications were prescribed by a des-
ignated clinical coordinator in each center,
who was not involved as a surgeon or exam-
iner. With this scheme, the investigators, the
examiners and the surgeons were blinded,
although the patients were not.
Randomization and Allocation concealment
All patients were recruited for comprehensive
dental care. Periodontal and endodontic
health was established prior to surgical inter-
ventions. Following a hygienic phase, all
patients were reevaluated for their oral health
and healing response to periodontal therapy,
and a surgical treatment plan was estab-
lished. Following this, the patients were
entered into the study using randomization
tables allocating the patient a number with a
corresponding envelope. The randomization
tables were prepared for each center sepa-
rately by a biostatistician (MCMW). Blocked
randomization was performed in blocks of
eight, whereby at every block of eight enroll-
ments, there were two subjects randomly
assigned to one of the four intervention
groups. The envelope contained the alloca-
tion to one of the four groups and was
opened 1 h prior to the surgical intervention
by a registered dental surgery assistant owing
to the fact that one test and the two control
groups had to take the medication prior to
implant placement. In this way, the alloca-
tion to one of the treatment groups remained
obscure to the operating surgeon.
Outcome variables
Subjects were examined clinically by cali-
brated examiners at week 1, 2, 4, and 8 follow-
ing implant installation for postoperative
complications. In addition, Visual Analogue
Scales (VAS) on a score of 0-10 were obtained
from the patients from day 1 through 7 and
day 14.
The surgeons involved had no access to the
data collection sheets or the group allocation,
while the examiners had no access to the
patients treatment records or group alloca-
tion.
The parameters examined included: